This present invention is directed to a novel process for the preparation of 2-[alkyl(aryl)]sulfonylbenzenesulfonyl chlorides and intermediates thereof.
2-[alkyl(aryl)]sulfonylbenzenesulfonyl chlorides are compounds known to be useful as intermediates in the production of certain herbicidal compounds as disclosed, e.g., in U.S. Pat. No. 4,783,285. These compounds are also known to be useful as intermediates in the preparation of compounds having activity as protease inhibitors as described, e.g., in PCT Patent Application Publication No. WO 97/36580. In light of the usefulness of these compounds in such production methods, there is a continued need to develop simpler and milder methods for their production.
To date, methods for producing 2-[alkyl(aryl)]sulfonylbenzenesulfonyl chlorides are not entirely acceptable. For example, U.S. Pat. No. 4,783,285 describes a four step process for the synthesis of 2-methylsulfonylbenzene sulfonylchloride which involves the oxidation of an aryl sulfide to an aryl sulfone with sodium periodate and the oxidation of an aryl sulfide to an aryl sulfonyl chloride with chlorine water. However, this method has been found to be disadvantageous since it requires the use of methyl mercaptan and involves the multiple oxidation steps noted above.
Accordingly, the need exists for a simpler, safer method for the production of 2-[alkyl(aryl)]sulfonylbenzenesulfonyl chlorides, which can be used on a large scale.
The present invention relates to a process for the preparation of 2-[alkyl(aryl)]-sulfonylbenzene sulfonyl chlorides of the formula: 
in which R is alkyl or aryl substituted at the ortho or meta positions with alkyl, aryl, NHAc or alkoxy, comprising the steps of:
a) reacting 2-chloronitrobenzene, 2-fluoronitrobenzene or 2-bromonitrobenzene with a compound of the following formula:
RSO2xe2x88x92M+
wherein R is defined above and M is sodium, potassium, lithium, ammonium or quaternary ammonium, in a polar aprotic solvent at a temperature of about 50 to 190xc2x0 C.;
b) reacting the material prepared in step (a) with hydrogen at a pressure of about 20 to about 60 psi in a polar aprotic solvent at a temperature of about 20 to about 60xc2x0 C.; and
c) diazotizing the material prepared in step (b) with sodium nitrite in the presence of hydrochloric acid and reacting the resulting diazonium salt with sulfur dioxide in the presence of copper (I) or copper (II) compounds or a mixture thereof, in water.
The present invention has utility in producing the desired compounds in higher yields through a shorter, simplified procedure in comparison to prior art processes. The present process further results in a product of higher purity in comparison to known processes, which eliminates the need for further purification. The present process is advantageously readily adaptable to large-scale production.
The present invention is directed to a process for the production of 2-[alkyl-(aryl)]sulfonyl benzenesulfonyl chlorides having the following formula: 
where R is alkyl or aryl substituted at the ortho or meta positions with alkyl, aryl, NHAc or alkoxy, comprising the following steps: 
wherein X is chlorine, fluorine, or bromine; M is sodium, potassium, lithium, ammonium or quaternary ammonium; and R is as defined above; 
Preferably, R is an alkyl of 1 to 8 carbons or aryl substituted at the ortho or meta positions with alkyl, aryl, NHAc or alkoxy. Most preferably, R is methyl. Preferably, X is bromine.
In reaction step (a), the 2-chloronitrobenzene, 2-fluoronitrobenzene or 2-bromonitrobenzene is reacted with the sulfinate salt of formula RSO2xe2x88x92M+ in a polar solvent. The solvent should be aprotic solvent, such as N,N-dimethylformamide, dimethylsulfoxide, N-methyl-2-pyrolidinone, or N,N-dimethylacetamide. Preferably, the solvent is DMSO. The reaction should take place at a temperature of between about 50 to about 190xc2x0 C., preferably between about 50 to 150xc2x0 C. and most preferably between about 75 to about 80xc2x0 C. The reaction should be run until completion, generally within 1 to 24 hours and preferably 1 to 3 hours. The product can be isolated by drowning the reaction mixture in water.
In reaction step (b), the hydrogenation of the nitrophenylsulfone may be run in methanol and dilute sulfuric acid or ethanol to provide aminophenylsulfone as its sulfate salt or as the free base. Preferably, this reaction is run in the presence of 5 to 10 mole percent of a Group VIII metal catalyst, such as Palladium or Rhodium, preferably, Palladium. Reaction step (b) is preferably run in ethanol at a pressure of 35 to 50 psi and a temperature of between about 20 to 40xc2x0 C. The reaction product from step (b) can be recovered by conventional techniques which will be recognized by one skilled in the art, e.g., filtering off the catalyst and evaporating off the excess solvent from the filtrate to yield the desired product.
Reaction step (c) comprises the diazotization of 2-methylsulfonylaniline with aqueous sodium nitrite in the presence of hydrochloric acid at a temperature of between about xe2x88x925 to about 10xc2x0 C., and preferably 0 to about 5xc2x0 C. This is followed by reaction with sulfur dioxide dissolved in acetic acid. The sulfur dioxide may be gaseous or liquid. Preferably this reaction takes place in the presence of catalytic amounts copper (I) chloride, copper (II) chloride dihydrate or a mixture thereof. The reaction time is generally about 2.5 to 3 hours for complete conversion. The product of reaction step (c) may be isolated via filtration and repeated washing with water to remove traces of the copper salts.
The present invention further encompasses a process for the production of the sulfone intermediate reaction product of reaction step (a). The sulfone intermediate has the following formula: 
wherein R is alkyl or aryl substituted at the ortho or meta positions with alkyl, aryl, NHAc or alkoxy;
Y is NO2, alkyl sulfate, aryl sulfate, CN, alkyl carbonate, aryl carbonate or CHO when in the 2-position; hydrogen, alkyl, aryl, NO2, alkyl sulfate, CN, alkyl carbonate, aryl carbonate, or CHO when in the 3,5 or 6-positions; and hydrogen, alkyl, aryl or CF3 when in the 4-position, which comprises:
reacting 2-chloronitrobenzene, 2-fluoronitrobenzene or 2-bromonitrobenzene derivatives having the Y group as defined above with a compound of the formula:
RSO2xe2x88x92M+
wherein R is as defined above and M is sodium, potassium, lithium, ammonium, or quaternary ammonium in a polar aprotic solvent at a temperature of about 50-150xc2x0 C.
As used herein, the terms xe2x80x9calkylxe2x80x9d and xe2x80x9calkoxyxe2x80x9d are meant to include both straight and branched chain moieties containing 1-8 carbon atoms. The term xe2x80x9carylxe2x80x9d is meant to include aromatic radicals of 6-12 carbon atoms. The term xe2x80x9chalogenxe2x80x9d is meant to include fluorine, chlorine, bromine and iodine.
The present invention will now be illustrated by reference to the following specific non-limiting examples.